NCT03774095

Effect of Dietary Oils as G-protein-coupled Receptor Agonists on Glucose Tolerance

Status unknown NA Last updated 14 December 2018

What this trial tests

NA trial testing Hydrolyzed pine nut oil in Type 2 Diabetes Mellitus in 10 participants. Status unknown.

Timeline

11 June 2018

Primary endpoint
30 December 2018

30 December 2018

Quick facts

Lead sponsor	Karina Vejrum Sørensen
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	treatment
Enrollment	10
Start date	11 June 2018
Primary completion	30 December 2018
Estimated completion	30 December 2018
Sites	1 location across Denmark

Drugs / interventions tested

• Hydrolyzed pine nut oil
• Hydrolyzed pine nut oil and olive oil

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →
• Obesity — all drugs for Obesity →

Sponsor

Karina Vejrum Sørensen

Who can join

Adults 40 to 70, any sex, with Type 2 Diabetes Mellitus or Obesity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Agonistic activation of fat metabolite responsive G-protein-coupled receptors (GPCR) has been linked to improved glucose metabolism through increased glucose-stimulated-insulin-secreting (GSIS) and incretin release, improved insulin sensitivity and reduced low grade inflammation. In vitro studies have demonstrated that pinolenic acid (20% of pine nut oil) is a potent dual agonist of two GPCRs: free fatty acid receptor-1 (FFA1, formerly GPR40) and free fatty acid receptor-4 (FFA4, formerly GPR120). Moreover, pinolenic acid was able to improve glucose tolerance in mice. G-protein-coupled receptor-119 (GPR119) is known to be activated by the monoacylglycerol: 2-oleoylglycerol (2OG), which is a glycerol molecule attached to oleic acid in the second position. Olive oil contains 61-80% oleic acid, and under digestion 2OG is produced. 2OG has been shown to stimulate GLP-1 release in humans and interestingly, it has recently been suggest that simultaneous activation of GPR119 and FFA1 acts in synergy and enhances enteroendocrine GLP-1 secretion more than the summarized individual agonistic activation. However, this remains to be evaluated in humans. The investigators hypothesize that a combination of pinolenic acid and 2OG administered in delayed release capsules will act in synergy and enhance 1) GLP-1 secretion by stimulating FFA1/FFA4 and GPR119 on enteroendocrine cells causing improved GSIS and increased satiety and 2) enhance GSIS by directly stimulating FFA1 and GPR119 on beta-cells.

Study aim: To investigate the acute effects of pinolenic acid combined with 2OG (olive oil) versus pinolenic acid alone on changes in glucose tolerance, insulin, GLP-1, GIP and ghrelin secretion, appetite and gastrointestinal tolerability in overweight and obese healthy humans.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Development of Free Fatty Acid Receptor 4 (FFA4/GPR120) Agonists in Health Science.
   Son SE, Kim NJ, Im DS. · · 2021 · cited 19× · PMID 33372166 · DOI 10.4062/biomolther.2020.213
2. Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases.
   Strassheim D, Sullivan T, Irwin DC, Gerasimovskaya E, et al · · 2021 · cited 11× · PMID 34943862 · DOI 10.3390/cells10123347